GROWTH OF B MALAYI IN MURINE MODELS--ROLE OF NK CELLS

在过去的几年里，我们一直在分析布鲁贾的进程 在许多小鼠模型中发现马来病毒感染。基于这些研究，我们 提出一种假说，即马来丝虫需要宿主来源的因子 哺乳动物宿主生长发育的淋巴起源。这 假设促使我们重新审视人与人之间的互动 免疫系统与马来丝虫作为一种动态的双向相互作用， 而不是纯粹的宿主保护性反应。我们的数据强烈表明 NK细胞是该因子的潜在细胞来源。在 目前的提议，我们计划通过重复一些 我们的研究，以及评估(1)NK细胞枯竭的效果 易感动物和(2)非允许动物的NK细胞重建 动物对马来丝虫生长的影响。此外，我们还将分析 马来丝虫在非放养动物体内损失的动力学研究 在其发展过程中需要增长因素的精确点。 我们还建议建立体外实验来鉴定一种细胞系 这将最好地支持马来丝虫的体外生长和发育。 利用标准的体细胞基因技术，我们将分离 细胞系中的许多变种不再支持生长 马来丝虫属(B.Malayi)。利用差异显示技术，我们将确定 突变体中缺失的信使核糖核酸(S)。 确定参与相互作用的分子(S)可能会有所帮助 美国制定了免疫预防的基本方法，以及 淋巴丝虫的药理学。

Over the past few years, we have been analyzing the course of Brugia malayi infection in numerous murine models. Based on these studies, we propose a hypothsis that B. malayi requires a host derived factor of lymphoid origin for growth and development in the mammalian host. This hypothsis provokes us to re-examine the interaction between the human immune system and B. malayi as a dynamic bi-directional interaction, rather than a pure host protective response. Our data strongly suggest that NK cells are a potential cell source for this factor. In the current proposal, we plan to confirm our hypothesis by repeating some our studies, as well as evaluating the effect of (1) NK cell depletion in susceptible animals and (2) NK cell reconstitution in non-permissive animals on the growth of B. malayi. In addition, we will analyze the kinetics of the loss of B. malayi in non-permissive animals to determine the precise point in its development that the growth factor is required. We also propose to set up in vitro experiments to identify a cell line that will best support the in vitro growth and development of B. malayi. Using standard somatic cell genetic technologies, we will isolate numerous variants from the cell line that no longer support the growth of B. malayi. Using differential display technology, we will determine the mRNA molrcule(s) that is (are) missing in the mutants. Identification of the molecule(s) involved in the interaction could help us formulate a rationale approach to immunoprophylaxis, as well as pharmacology of lymphatic filarial parasites.